This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Structure and function of TRP family channels. We have used cyo-EM and single particle analysis to determine structures of ion channels of the TRP family. Those studied included TRPV1, the receptor for painful heat that also senses the active ingredient in hot chili peppers, capsaicin, TRPV2, another heat sensor, and TRPY1, an ion channel of the yeast vacuole that releases calcium into the cytoplasm in response to osmotic stress. We have also used cryo-EM to characterize vesicles into which TRP channels been reconstituted, which allowed us to quantify the activity of the reconstituted channels. The TRP family of non-selective cation channels represent one of the most important classes of ion channels for human physiology, and constitutes a major class of drug targets. Our work represents the first reliable three-dimensional structural information available for any full-length TRP chanels, and also the first quantitative assays of purified and reconstituted TRP channels.